PB2457: RUXOLITINIB AS TREATMENT IN PATIENTS WITH ACUTE AND CRONIC GRAFT-VERSUS-HOST DISEASE. REAL WORLD EVIDENCE
Authors: Francisco José Jiménez Nájar, Belén Olivares Pérez, Alicia Aguirre Lora, Noelia Romero Mata, Estefanía García Torres, Carmen Martín Calvo
Journal: HemaSphere (2023)

Topic: 22. Stem cell transplantation - Clinical Background: Allogeneic haematopoietic cell transplantation (HSCT) is a potentially curative treatment for haematological malignancies, but is not without complications. The major cause of transplant-associated mortality is graft-versus-host disease (GVHD). Its standard of care for both acute and chronic forms is corticosteroids. Unfortunately, up to 50% of cases become resistant to corticosteroids. Ruxolitinib is a selective inhibitor of JAK-kinases, which play a key role in the regulation of the immune system, and has shown efficacy in the treatment of corticosteroid-dependent or resistant GVHD. Aims: -To show our experience in the use of Ruxolitinib as a second line treatment in GVHD. -To describe the efficacy of the treatment in our patients. -To estimate overall and progression-free survival. Methods: We conducted an observational and retrospective study of 40 patients undergoing HSCT at our centre from April 2016 to September 2022 treated with second-line Ruxolitinib. We analysed transplant-related variables, acute and chronic GVHD (aGVHD and cGVHD), infections during treatment, as well as toxicity and progression-free survival (PFS) and overall survival (OS). IBM SPSS Statistics v.20 was used to perform the statistical analyses. Results: A total of 40 patients received Ruxolitinib as 2nd line treatment of GVHD initially in addition to corticosteroid therapy, for aGVHD (17 patients, 42.5%) or cGVHD (23 patients, 57.8%). The median follow-up of the series is of 35 months (4.7-120). The characteristics of HSCT are shown in table 1. In the aGVHD group, (Table 2) 47% of patients were treated with Ruxolitinib for corticodependence. Forty-seven % of patients had GVHD grade 3 at the time of treatment initiation. The median duration of treatment was 2 months (8 days-14 months); 35% of patients were concomitantly treated with photopheresis. Eleven (65%) patients achieved complete response. CMV reactivation occurred in 5 patients (29%) and there was no fungal infection. In 4 (23.5%) of the patients there was progression of the underlying disease. Five of the patients (29%) died, most frequently due to aGVHD (60%). The median progression-free survival (PFS) is 27 months (8-46.5), with an estimated 2-year probability of 50% (±15.2%). For overall survival (OS), the median was not reached and the estimated 2-year probability is 54% (±15.8%). Among patients with cGVHD (table 2), ruxolitinib was added in 44% of cases due to lack of improvement with corticosteroid therapy (no criteria for steroid-refractory) and in 30% due to corticodependence. The median duration of treatment was 7 months (24 days-58 months). 84% of patients had moderate or severe cGVHD; the response rate was 74% (57% partial response). Unlike aGVHD cases, the infection rate was higher in this group (52%), with fungal infections ocurring in 26% of cases. CMV was reactivated in only 2 cases. In 3 (13%) of the patients there was progression of the underlying disease and 8 patients died (35%), with bacterial and fungal infections being the most frequent cause of exitus. The median PFS is 102 months (56-149.5), with an estimated 2-year probability of 78% (±8.6%). Median OS is 102 months (75-131), with an estimated 2-year probability of 87% (±7%). Summary/Conclusion: GVHD remains the leading cause of non-relapse mortality, so it’s necessary to initiate early treatment and to have alternatives when first-line treatment fails. In our series, Ruxolitinib is an effective and well-tolerated drug for second-line treatment of aGVHD and cGVHD, and its effectiveness allows a faster withdrawal of corticosteroid therapy. In our patients, Ruxolitinib in cGVHD is mostly started in severe cases, perhaps too late. More studies are needed to assess the efficacy of the drug with an earlier use.Keywords: Graft-versus-host disease (GVHD), Real world data, Ruxolitinib, Allogeneic bone marrow transplant